A spike in blood glucose level occurs following each significant meal: breakfast, lunch or dinner, as the carbohydrates in a meal convert to glucose and the glucose from the blood stream enters the cells. A glucose spike is defined as the highest blood glucose level after a meal minus the pre-meal glucose level. Resulting from a step input of carbohydrates to the human digestive system, a post-prandial or post-meal glucose spike may occur following breakfast, lunch or dinner, causing three spikes and three perturbation periods (top half of FIG. 1). A perturbation period is defined as the post-meal time period during which the blood glucose level increases above the pre-meal level, going through a maximum before approaching the pre-meal glucose level. The increase in area under the glucose concentration vs. time plot in the perturbation period over the pre-meal area can be taken as a measure of the glucose shock experienced by the vital organs and systems in the body.
The time of occurrence of the glucose spike (tspike), as shown in FIG. 1, and its amplitude, defined as the maximum increase in glucose level over the pre-meal glucose, depend on the type and amount of carbohydrates ingested, a person's metabolism and insulin delivery system.
The body cells need glucose for energy, but higher than normal level of glucose in the blood imparts a glucose shock that may lead to adverse health conditions or life-threatening diseases, including but not limited to, obesity, abdominal fat, hair loss, pre-diabetes, diabetes, hypoglycemia, cardiovascular diseases, aging, Alzheimer's disease, dementia, free-radical-related diseases, or cancer.
Obesity is becoming a significant health risk all over the world. In the USA, 31% of the population is considered obese and 300,000 deaths annually are linked to obesity. Obesity is measured by the percentage of the body weight that is fat. Men with more than 25 wt % body fat, and women with more than 30 wt % body fat are considered obese. Obesity is also measured by the body mass index (BMI), which is defined as the body weight in kilograms by the square of height in meters. A person with a BMI of 30 or more is considered obese. There is a strong correlation between obesity and the occurrence, of Type 2 diabetes. Obesity in mid-life increases the risk of developing Alzheimer's disease by a factor of 3.5. Moreover, abdominal fat in obese or non-obese people is linked to diabetes and cardiovascular diseases like heart attack and stroke. Elevated lipids (fats) in the blood also damage beta-cells that produce insulin needed for glucose uptake by cells. There then is a need for a method for managing obesity and reducing abdominal fat.
Diabetes, caused by high blood glucose level in the blood stream, is a serious illness affecting close to 28 million in the USA and 250 million worldwide. About 50 million in the USA are pre-diabetic. Blindness, kidney disease (nephropathy), nerve damage (neuropathy), stroke, heart attack, and leg amputation are some of the menaces of diabetes. Every year millions succumb to cardiovascular complications resulting from diabetes. Disease of the retina (retinopathy), caused by diabetes, is the main cause of sight loss in working age adults. There then definitely is a need for a method for lowering the risk of developing diabetes, or managing diabetes, if already developed.
Blood glucose level is controlled by insulin, a hormone released by the pancreas into the blood. From the blood, the insulin enters the cells, from where it brings the glucose receptors (GLUT-4) to the cell membranes that are in contact with the blood stream. It is through the GLUT-4 that the blood glucose enters the cells.
In a Type 1 diabetic patient, insulin is not produced, necessitating the injection of synthetic insulin as a life-saving measure. In a Type 2 diabetic patient, insulin is not produced in sufficient amounts, or the body cells resist the absorption of insulin—a condition known as insulin resistance—both of which may lead to inefficient glucose uptake by the body cells, causing a condition termed as impaired glucose tolerance (IGT). IGT raises the blood glucose above the normal level of 6 mmol/L, measured after 12-hour of fasting. Two units are used for the blood glucose level: mmol/L (used in Canada, Europe, India, and China) or mg/dL (used in USA). A multiplication by 18 of the blood glucose level number in mmol/L is needed to obtain the glucose level in mg/dL.
To manage Type 2 diabetes, the prior art guidelines recommend monitoring the 12-hour fasting and the two-hour after-meal blood glucose levels. These guidelines, however, fail to recognize the adverse long-term effects of exposing the vital body organs and systems to a glucose spike or a glucose shock occurring within the first two hours of taking a meal.
The high blood glucose level in Type 2 diabetes is controlled through medicine (prescribed or alternative), exercise, and diet. Some medicines may have adverse health effects on some patients. The exercise and the diet plans recommended by prior art are general guidelines that do not take into account a person's carbohydrate intake, body metabolism and insulin delivery system. What may work for one person may not work for another. These general guidelines recommend taking low glycemic index (GI) and low glycemic load (GL) food, and performing exercise, but do not provide any quantitative method for tailor-making a meal plan or an exercise plan for an individual. The term glycemic index (GI) is defined as the potential of a food item to raise the blood glucose level relative to that by 100% glucose. The term glycemic load (GL) for a food item is defined as the product of GI of the item and its carbohydrate content in grams. The prior art guidelines do not recommend the reduction of post-prandial glucose spike or glucose shock, nor do they recommend performing post-prandial exercise as a way of controlling the glucose spike or glucose shock. There then is a definite need for a person-specific, quantitative method for lowering the risk of developing, or if already developed, managing, diabetes, using less or no medicine.
Hair loss or hair thinning in diabetic patients has been linked to high blood glucose that restricts the blood flow and nutrients supply to the hair roots and follicles. Although not a life-threatening health condition, hair loss can cause a significant psychological distress, especially to women.
Elevated blood glucose level may also accelerate aging-related diseases, including but not limited to, cognitive or memory decline. For example, memory decline has been linked to elevated glucose level by researchers from the Taub Institute for Research on Alzheimer's disease and the aging brain at Columbia University Medical Center. These researchers found that elevated blood glucose adversely affects the dentate gyrus, a sub region of the hippocampus, which is a delicate brain structure vital to human memory (WU et al., “The Brain in the Age of Old: The Hippocampal Formation is Targeted Differentially by Diseases of Late Life”, Annals of Neurology, Vol.: 64, Issue: 6, pages: 698-706, Dec. 23, 2008). The risk of developing Alzheimer's disease, an aging-related disease, increases by a factor of 3.5 and 2, respectively, with obesity and diabetes, both of which are linked to elevated blood glucose levels. Aging-related diseases affect the wellness of a person, while placing an enormous psychological and financial burden on families and the health care system. There is a need for reducing the risk of developing aging-related diseases caused by elevated blood glucose levels.
Body's inability to absorb insulin secreted by the pancreas in response to the post-prandial glucose spike may lead to elevated blood insulin level that may adversely affect the functions of the vital organs and systems, including promotion of cellular growth or cancer. A study by researchers at Albert Einstein College of Medicine of Yeshiva University found that higher-than-normal levels of insulin place postmenopausal women at an increased risk of breast cancer (GUNTER et al., “Insulin, Insulin-Like Growth Factor-I, and Risk of Breast Cancer in Postmenopausal Women”, Journal of National Cancer Institute, Vol.: 101, No.: 1, pages: 48-60, Jan. 7, 2009). Elevated insulin level also decreases DHEA (dehydroepiandrosterone), a hormone that is conducive to longevity, and may increase beta-amyloid, a protein that builds up in the brains of patients with Alzheimer's disease. Elevated blood glucose level is also linked to Alzheimer's disease. Hence there is a need for reducing high insulin level in the blood by controlling the post-prandial glucose spike or glucose shock.
Blood glucose may also generate free radicals linked to cell abnormalities, including cancer (DONNINI et al., “Glucose may Induce Cell Death through a Free Radical-Mediated Mechanism”, Biophysics Research Communication, Vol.: 219, Issue: 2, pages: 412-417, Feb. 15, 1996).
Post-prandial glucose spike may also cause reactive hypoglycemia. Hypoglycemia is a condition in which excessive insulin release by the pancreas in response to a glucose spike leads to a dangerously low glucose level in the blood. Heart fibrillation, dizziness, tremors and coma are some of the ill effects of hypoglycemia. Eating more carbohydrates to raise the sugar level may be a quick fix, which in the long run may be detrimental to the pancreas and other organs. There then is a need for a more effective method of managing hypoglycemia.
Elevated blood glucose level measured two hours after a meal may cause cardiovascular diseases even in non-diabetic patients whose fasting glucose level is normal (LEUNG, “Cardiovascular Disease and Post-prandial Hyperglycemia: A Cardiologist's Perspective”, The Federation of Medical Societies of Hong Kong, Medical Bulletin, Vol.: 15, No.: 6, Pages: 14-15, June 2010). Since the post-prandial glucose maximum may be higher than the glucose level at two hours after a meal, the risk of cardiovascular diseases in non-diabetic patients subjected to post-prandial glucose spike may be even higher than that reported by Leung. Diabetic patients are even more susceptible to cardiovascular diseases. There is a need for controlling blood glucose spike or glucose shock to lower the risk of cardiovascular diseases in diabetic or non-diabetic patients.
The background information underscores the need for a person-specific, quantitative method for reducing blood glucose spike or glucose shock to lower the risk of developing, or to manage, if already developed, the various glucose-spike-induced diseases and adverse health conditions. The instant invention provides such a method for lowering the risk of developing, or managing, if already developed, diseases, including but not limited to, obesity, abdominal fat, pre-diabetes, diabetes, hypoglycemia, aging, cardiovascular diseases, or cancer.
The invention culminated from an adversity when one of the inventors was initially alerted about being pre-diabetic and later diagnosed with Type 2 diabetes, because of higher than normal 12-hour fasting glucose level and symptoms of numbness in fingers, toes and around the skull. Having just completed 13 consecutive marathons—training regularly and running at least one marathon a year—over 10 years, the runner was shocked to realize that the prior-art-prescribed meal plan and the strenuous physical activities fell short in keeping the blood glucose level within a normal range.
The invention was conceived of when the human digestive system, a complex reactor, was compared with a simpler industrial reactor. An industrial reactor is fed at a constant injection rate to ensure target product rate and quality, and to avoid adverse reactor conditions, such as temperature excursion, reactor damage, or even reactor shutdown. By contrast, the complex human digestive system is fed in three step functions through three significant meals: breakfast, lunch and dinner, subjecting the system to three post-prandial glucose spikes or glucose shocks, and three glucose perturbation periods (top half of FIG. 1). These spikes or shocks repeated daily since childhood may lead to various adverse health conditions or life-threatening diseases.
As described in Examples 1 and 2 later in this disclosure, by controlling the post-prandial glucose spike or glucose shock following the method of this invention, the runner was able to lose body weight and abdominal fat, bring down blood glucose level from the Type 2 diabetic level to the normal range, and assuage some symptoms of aging.